Revenue-generating satellite TV service announced.
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Commerce↗
Biomedical subjects
B Fisher
Publications and source records attributed to B Fisher.
Tumor size and regional lymph node metastasis in colorectal cancer. A preliminary analysis from the NSABP clinical trials.
This study explores the relationships between tumor size and regional lymph node involvement in patients with Dukes' B and C colorectal cancer in the randomized prospective clinical trials of the NSABP. Six-hundred and seventy patients with colon cancer and 236 patients with carcinoma of the rectum were available for analysis. Utilizing cumulative frequency distributions of tumor diameter and tumor volume, comparisons were carried out between Dukes' B and C lesions. The results indicate that there was no correlation between the longest diameter of the primary tumor and the status of regional lymph nodes for either colon or rectal cancer. Moreover, this lack of association was evident throughout the distribution. When tumor volume was analyzed, Dukes' B tumors proved to be consistently larger than Dukes' C lesions. This inverse relationship was statistically significant for carcinoma of the rectum. These findings underscore the unique biological behavior of colorectal cancer and emphasize the function of the current generation of randomized prospective trials in providing natural history information.
Clinical Trials as Topic↗
Pathologic findings from the National Surgical Adjuvant Breast Project. VIII. Relationship of chemotherapeutic responsiveness to tumor differentiation.
The possible influence of histologic grade, necrosis and size of invasive breast cancers on the five year survival rate of women treated in NSABP clinical trials with regimens of L-PAM (P) and L-PAM + 5-FU (PF) and for four years in those receiving L-PAM + 5-FU + methotrexate (PMF) was investigated. Generally, all regimens effected an increased survival when compared to controls that did not receive adjuvant therapy. However, this favorable response was statistically more pronounced in those women whose cancers were histologically evaluated to be poorly differentiated (histologic grade 3) and exhibited four or more regional axillary nodal metastases. Patients whose cancers were associated with 1-3 nodal metastases were not found to exhibit statistically significant responsiveness to any regimen regardless of tumor grade. Possible reasons for this dichotomy are presented. Tumor necrosis, although paralleling the results noted with histologic grade, failed to further discriminate patients who might respond to chemotherapeutic agents. Tumor size was not found to be a consistently significant indicator of chemotherapeutic responsiveness. Generally, the PF and PMF regimens were more effective than P alone in those patients exhibiting a response. These findings indicate the importance of identifying subsets of patients with breast cancer not only from a biologic but also therapeutic perspective.
Adult↗
Scar cancers: pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4) - IX.
The uncomplicated non-encapsulated sclerosing lesion (NESL) or radial scar of breast is a banal lesion which may be confused with tubular carcinoma. Yet, that the latter may arise in such scars is strongly suggested by the recognition of examples portraying morphologic features consistent with such 'early' transformation. Further, 38% of 1569 cases of unequivocal invasive breast cancers from patients enrolled in the National Surgical Adjuvant Breast Project, protocol 4, were found to be associated with scar. The scar in 14% of these was strikingly similar if not identical morphologically with the NESL or radial scar (type 1 scar cancer). Four other types of scar were identified. It is uncertain whether these represent variations of the NESL or are unique. However, each type possessed some distinguishing pathologic characteristics as disclosed by contingency table analyses of 36 histopathologic and 6 clinical features of these cancers. Most importantly, 6-year postmastectomy survival was significantly better as revealed by life-table analyses for patients whose cancers were designated as types 1 and 4 than for those with other scar types or in whom their cancer lacked scar. This relationship was found to be independent of nodal status. Ductal obliteration, a common finding in the banal NESL and scar cancers, has been previously suggested to play a role in their evolution. Our observations indicate that vascular obliterative alterations may be equally or perhaps even more significant in this regard. This as well as other features suggests an analogy between them and so-called scar cancers of the lung. Attention is directed to the prognostic significance of type and degree of tubule formation observed in some breast cancers. The results suggest a revision of the scheme utilized for the histologic grading of breast cancers. However, it appears valid to simply categorize breast cancer into well-differentiated (histologic grades 1 and 2) and poorly differentiated (histologic grade 3) types. Our data does not support the hypothesis that tubular cancer may 'progress' into less differentiated forms.
Adenocarcinoma↗
Relation of estrogen and/or progesterone receptor content of breast cancer to patient outcome following adjuvant chemotherapy.
In 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a prospectively randomized clinical trial to evaluate the relative merits of 1-phenylalanine mustard and 5-fluorouracil (PF) with and without tamoxifen (T) as adjuvant therapy for patients with primary breast cancer and positive axillary nodes. A previous presentation of findings noted that there was a strong relationship between the outcome of those receiving PFT and the estrogen receptor (ER) and progesterone receptor (PR) content of their tumors. This report relates the outcome of the PF-treated patients in that trial with these tumor receptors. It indicates that the results observed following nonhormonal therapy (PF) are also related to tumor receptors. Both the disease-free survival (DFS) and survival (S) of women following PF therapy were influenced by the ER and PR content of their tumors. Subsequent to adjustment for other prognostic variables, the predictive influence of tumor ER persisted. Both the DFS (p = 0.0003) and the S (p = 0.00003) were significantly higher in those with greater than or equal to 10 fmol tumor ER than in those with less than 10 fmol ER. The PR significantly added to the predictive value of ER. Thus, this analysis is the first to demonstrate that having information on both ER and PR is important for predicting outcome of patients receiving adjuvant chemotherapy. The study does not provide information which correlates receptor status with the response of patients to adjuvant chemotherapy since there is no similar nonchemotherapy-treated group of patients in the trial. The findings continue to emphasize that there is a heterogeneity in outcome of breast cancer patients to adjuvant chemotherapy which is related to an increasing number of host and tumor variables. For proper assessment of overall results, it is essential that analyses employ tests for interaction to indicate homogeneity or heterogeneity of patient subsets and that adjustments be made for imbalances in tumor ER and PR as well as in other prognostic factors.
Antineoplastic Combined Chemotherapy Protocols↗
Treatment of primary breast cancer with L-PAM/5-FU and tamoxifen: an interim report.
This trial studied the possibility that tamoxifen, added to L-phenylalanine mustard and 5-fluorouracil, enhances the established benefit of the latter two drugs in treatment of women with breast cancer and positive axillary nodes. The addition of tamoxifen resulted in a 25% decrease in treatment failure at 24 months and a 23% decrease at 36 months. In patients greater than or equal to 50 years old, there was a 48% reduction at 24 months and a 39% reduction at 36 months. This advantage was statistically significant at both two and three years' follow-up (p less than 0.001). Higher receptor levels were associated with a greater probability of disease-free survival. Patients less than or equal to 49 years old were less responsive. There was some evidence at 24 months that patients in this age group with four or more positive nodes who also had high ER levels might benefit from tamoxifen. At 36 months, however, this benefit was no longer evident. This form of adjuvant therapy is not recommended in patients less than or equal to 49 years of age whose tumor estrogen and progesterone levels are below 10 fmol; there is an appearance of benefit in patients greater than or equal to 50 with low estrogen and progesterone levels, and stronger evidence of benefit when these levels are high among the older group of patients.
Age Factors↗
Adjuvant chemotherapy in stage-II breast cancer: an overview of the NSABP clinical trials.
Data derived from 1848 patients entered into three adjuvant chemotherapy protocols are presented. The three studies were performed sequentially and were designed to identify patient subsets responding to one, two, or three chemotherapeutic agents. Comparison of disease-free survival in patients receiving L-PAM or placebo disclosed that L-PAM was beneficial in patients less than or equal to 49 years of age, but not in women greater than or equal to 50 years. Further analysis indicated that the subset of patients less than or equal to 49 years with 1-3 positive nodes sustained the greatest increment in disease-free survival with single-agent L-PAM. The addition of 5-FU to L-PAM was superior to L-PAM alone in patients greater than or equal to 50 years of age, particularly those with greater than or equal to 4 positive nodes. The three-drug combination of L-PAM, 5-FU, and methotrexate failed to provide a benefit over and above that achieved by the L-PAM-5-FU combination in all subsets examined. The results underscore the heterogeneous response to chemotherapy demonstrated by patient subsets characterized on the basis of age and nodal status. The implications of the findings relative to the current status of adjuvant therapy are discussed.
Adult↗
Winds of change in clinical trials--from Daniel to Charlie Brown.
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Antineoplastic Agents↗
The prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Findings from the NSABP clinical trials.
The present study examines the prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Data were obtained from 1021 patients entered into two randomized prospective clinical trials of the NSABP. Tumor location proved to be a strong prognostic discriminant. Lesions located in the left colon demonstrated the most favorable prognosis. Tumors of the rectosigmoid and rectum had the worst prognosis with the relative risk of treatment failure for the latter being over three fold that of the left colon. When the relative risks associated with tumor location were adjusted for nodal imbalances, the left colon continued to demonstrate the most favorable prognosis. The presence of bowel obstruction also strongly influenced the prognostic outcome. Examination of the data without considering tumor location disclosed that patients with bowel obstruction were at greater risk for treatment failure than those without obstruction. The effect of bowel obstruction was influenced by the location of the tumor. The occurrence of bowel obstruction in the right colon was associated with a significantly diminished disease-free survival, whereas obstruction in the left colon demonstrated no such effect. This phenomenon was independent of nodal status and tumor encirclement, the latter two factors proving to be of prognostic significance independent of tumor obstruction. A multivariate analysis in which the covariate effects of sex, age, nodal status, tumor obstruction, encirclement, and tumor location were adjusted underscored the role of tumor location and obstruction as prognostic discriminants. The results indicate that the definition of prognostic factors can identify patient subsets with unique characteristics.
Carcinoma↗
Analysis and microbiological stability of an isosorbide 50% mixture.
Isosorbide mixture containing 50% w/v isosorbide and 5% w/v sorbitol is used in the treatment of hydrocephalus. The G.L.C. analysis of the mixture is described and its antimicrobial properties investigated. Results for the determination of lead in the mixture are given and the significance of the levels discussed with relevance to the treatment of infants.
Bacteria↗
Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.
In 1977 the National Surgical Adjuvant Breast and Bowel Project initiated a prospectively randomized clinical trial for women with primary operable breast cancer and positive axillary nodes. In this study 1891 patients were randomized to receive L-phenylalanine mustard and 5-fluorouracil (PF) either with or without tamoxifen (T). In this interim report findings are presented concerning disease-free survival (DFS) and survival as related to age and to estrogen receptor (ER) and/or progesterone receptor (PR) content of the tumor. The median follow-up time is 3 yr. Patients 50 yr of age or older with either 1-3 or more than 3 positive axillary nodes had a markedly longer disease-free survival on PFT than did those receiving PF adjuvant therapy (p less than 0.001). The effectiveness of PFT was related to the levels of tumor receptors. Patients 50 yr old or more with both tumor ER and PR levels of 10 fmole or more ("high") displayed the greatest benefit in disease-free survival from PFT (p = 0.004). Analyses by age indicated that it is more appropriate to divide patients of 50 yr or older into two age groups, 50-59 and 60-70 yr old. In the former the survival results were poorer on PFT when tumor PR was low, whereas, regardless of receptor levels, those 60-70 yr old experienced an advantage on PFT. In women under 50 yr of age, there was no difference in disease-free survival (p = 0.64), but survival results favored the PF over the PFT treated (p = 0.06). Patients under 50 yr with tumor ER and PR levels under 10 fmole ("low") had a poorer survival when given PFT (p = 0.003). Those whose tumors demonstrated a high ER and a low PR also had a shorter survival on PFT (p = 0.01). The observation of no benefit in younger patients when both receptor levels were high, but a benefit in older patients with receptor-poor tumors, indicates that, at least according to the conditions of this study, the difference between the two age groups cannot be explained by the association of age with receptor content. Multivariate analyses considered the effects of the number of positive nodes, age, ER, and PR. They support the conclusion that, while nodes and ER exert strong prognostic influences in both PF- and PFT-treated patients, the PR content of tumors is a stronger predictor of the effectiveness of PFT therapy than is ER content.(ABSTRACT TRUNCATED AT 400 WORDS)
Age Factors↗
Breast cancer estrogen and progesterone receptor values: their distribution, degree of concordance, and relation to number of positive axillary nodes.
Increasing evidence indicates the importance of ascertaining the quantitative estrogen receptor (ER) and progesterone receptor (PR) content (in femtomoles per milligram cytosol protein) of primary breast cancers. Those values obtained from the tumors of 1,887 patients participating in National Surgical Adjuvant Breast and Bowel Project protocol B-09 have been analyzed to define (1) the distribution of tumor ER or PR according to patient age, (2) the distribution of tumor PR within a specific ER interval, and (3) the concordance of tumor ER and PR levels. The present findings indicate how predictive the knowledge of the amount of one receptor (e.g., ER) may be for estimating the amount of the other (PR), when the latter is unknown.
Age Factors↗
Hemangiopericytoma of the pituitary fossa: case report.
A case of hemangiopericytoma presenting as a sellar and suprasellar mass is reported. Although this is the first report of this tumor in such a location, it appears similar to hemangiopericytomas found in other locations.
Female↗
Current sickle cell screening program for newborns in New York City, 1979-1980.
The newborn screening program mandated by the New York State Public Health Law requires that every baby born in the state be tested for eight conditions including sickle cell anemia. Although sickle cell screening of newborns has been in operation since 1975, the follow-up program for case retrieval to obtain repeat blood samples for definitive diagnosis and referral of diagnosed patients for ongoing medical care was established only in 1979. Of the 106,565 blood samples tested in New York City Newborn Screening Laboratory, March 1, 1979 to February 29, 1980, 141 infants were identified on repeat blood testing as having various forms of sickle cell disease (SS, SC and S beta-Thalassemia) and were referred for ongoing medical care. Data received on 131 patients from follow-up clinics revealed that the disease diagnosis made by the Newborn Screening Laboratory was confirmed in all patients. There were no deaths reported among the study patients (131 infants) followed for the period of 8-20 months despite the life-threatening complications among eight patients. Binomial distribution of the data on Black infants according to the Hardy-Weinberg equation showed reasonable agreement between the observed and computed incidence of various forms of sickle cell disease.
Anemia, Sickle Cell↗
Spirogermanium: effects on hematopoietic stem cells and survival of normal and tumor-bearing mice.
The effect of spirogermanium (SG) on hematopoietic stem cells, tumor burden, and survival times was investigated in C3H mice with transplanted mammary carcinoma. Compared to normal mice, the number of hematopoietic stem cells, or colony-forming units per spleen (CFU-S), was lower in the marrow of tumor-bearing mice. Spirogermanium at 15 and 30 mg/kg was not toxic to the normal hematopoietic cells in the marrow of either normal or tumor-bearing mice. In contrast to animals treated with cyclophosphamide, SG did not decrease the tumor growth rate or prolong the survival times of tumor-bearing C3H mice. Doses of 35-40 mg/kg SG did not prolong the survival times or decrease the tumor burden of AKR/J mice with a long-passaged lymphoma. These studies demonstrate that SG has minimal inhibitory effects to the marrow of normal mice and may promote the maintenance of normal marrow cells in tumor-bearing animals. However, in two different transplanted tumor cell lines, SG did not inhibit tumor growth or prolong host survival time.
Animals↗
The methodologic dilemma in retrospectively correlating the amount of chemotherapy received in adjuvant therapy protocols with disease-free survival.
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Antineoplastic Combined Chemotherapy Protocols↗
The interdependence of laboratory and clinical research in the study of metastases.
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Animals↗
Interrelation between tumor cell proliferation and 17-fluoresceinated estrone binding following primary tumor removal, radiation, cyclophosphamide, or tamoxifen.
The proportion of single intact viable mouse mammary tumor cells containing estrogen receptor (ER) as determined by 17-fluoresceinated estrone binding and the proportion labeled with [3H]thymidine (LI) have been assessed in the same cell population after either primary tumor removal, radiation, cyclophosphamide, or tamoxifen administration. Subsequent to tumor removal, the increase in LI occurring in a cell population from a residual tumor focus was associated with a concomitant decrease in the proportion of cells demonstrating 17-fluoresceinated estrone binding (fluorescence). As the level of LI in the tumor focus returned to that observed prior to tumor removal, the proportion of ER-containing cells simultaneously reverted to its original value. Following cyclophosphamide administration, there was a decrease in tumor LI and a concomitant elevation in the proportion of fluorescent cells which were dose related. The prolonged depression in LI following radiation was accompanied by a sustained increase in the proportion of ER-containing cells. Thus, the change in ER-containing cells was related to the alteration of the proliferating cell population by the various therapies. The findings support the thesis that fewer cells in the growth fraction of the tumor studied contain ER than in the nonproliferating cell pool. Following tamoxifen administration, a decrease occurred in the proportion of fluorescing cells due to competitive binding. There was no alteration in LI. This observation is not in conflict with the thesis that there is a correlation between ER and LI since the mechanism for reduction in detectable ER is different. These studies provide additional support to the credibility of the use of 17-fluoresceinated estrone binding for the determination of ER in individual tumor cells. They also indicate the usefulness of the method for obtaining biological information regarding tumor ER which cannot be obtained with the use of conventional biochemical analyses.
Animals↗